Article: Fluticasone

Fluticasone
Systematic (IUPAC) name
6,9-difluoro-11-hydroxy-16-methyl-3-oxo-17- (1-oxopropoxy)-androsta-1,4-diene-17-carbothioic acid (6α,11β,16α,17α)- S-(fluoromethyl) ester
Identifiers
CAS number	80474-14-2
ATC code	D07AC17 R01AD08, R03BA05
PubChem	444036
DrugBank	APRD00065
Chemical data
Formula	C25H31F3O5S
Mol. weight	500.572 g/mol
Pharmacokinetic data
Bioavailability	0.51% (Intranasal)
Protein binding	91%
Metabolism	Intranasal- hepatic cytochrome p450,3A4
Half life	10 hours
Excretion	renal
Therapeutic considerations
Pregnancy cat.	Category C for Intranasal and Inhaled
Legal status
Routes	Intranasal, Inhaled, Topical Cream or Ointment

Fluticasone propionate is a glucocorticoid often prescribed as treatment for asthma and allergic rhinitis. It is marketed with the brand name Flixotide® and Flixonase® by Allen & Hanburys and Flovent® and Flonase® by GlaxoSmithKline.

How it works

The precise mechanisms of glucocorticoid action in asthma are unknown. Inflammation is recognized as an important component in the pathogenesis of asthma. Glucocorticoids have been shown to inhibit multiple cell types (e.g., mast cells, eosinophils, basophils, lymphocytes, macrophages, and neutrophils) and mediator production or secretion (e.g., histamine, eicosanoids, leukotrienes, and cytokines) involved in the asthmatic response. These anti-inflammatory actions of glucocorticoids may contribute to their efficacy in asthma. Typically, however, the action on the cells affected requires several days. Therefore, inhaled steroids are not used for immediate relief of asthma, but instead as preventive and maintenance therapy.

Flonase dosage

Adults: The recommended dosage for adults is two sprays in each nostril daily. This is equivalent to 100 micrograms of fluticasone propionate in each nostril daily. After a few days and a decrease in symptoms, patients may be able to reduce their dosage to one spray, or 50 micrograms, in each nostril daily.

Adolescents and children (4 years and older): The recommended dosage for patients 4 years of age or older is one spray (50 micrograms) in each nostril daily. If patients do not seem to be responding to this dosage and symptoms are still present, the dosage may be increased to two sprays (100 micrograms) in each nostril daily. The maximum total daily dosage should not exceed 200 micrograms per day (2 sprays per nostril daily).

Flonase patent issues

GlaxoSmithKline's patent on Flonase expired on May 2004. As a direct result of this fact, the Food and Drug Administration (FDA) approved the sale of a generic version of Flonase on February 22, 2006. On February 23, 2006, GlaxoSmithKline (GSK) was able to obtain a temporary 10 day restraining order from a federal judge in Baltimore blocking the shipment and sales of the approved generic versions of Flonase. The restraining order would last until March 6, 2006. The basis of GSK’s complaints was that the FDA failed to follow its own regulations in approving the generics and failed to apply the same quality standards for the generic version as it did for Flonase. GSK made these arguments in petitions filed with the FDA, but the FDA rejected those petitions. Unfortunately for GSK, the Maryland District Court denied its request to extend the ban on Flonase generics beyond March 6, 2006. This ruling meant that generic versions of Flonase could now be sold.

Clinical trials

This listing is NOT complete and should NOT be construed as support for treatment decisions. See also PubMed clinical manuscripts referring to fluticasone

• Burge, P.S.; Calverley, P.M.; Jones, P.W.; Spencer, S.; Anderson, J.A.; and Maslen T.K. (2000). Randomised, double blind, placebo controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDE trial. British Medical Journal 320 (7245), 1297-1303. PMID 10807619.
• Paggiaro, P.L.; Dahle, R.; Bakran, I.; Frith, L.; Hollingworth, K.; and Efthimiou, J. (1998). Multicentre randomised placebo-controlled trial of inhaled fluticasone propionate in patients with chronic obstructive pulmonary disease. The Lancet 351 (9105), 773-780. PMID 9519948.

both support a positive outcome for use of fluticasone in patients with chronic obstructive pulmonary disease, also referred to as COPD